We studied the interaction of the progesterone receptor with the MMTV promoter in living cells, and found a pronounced ligand effect on mobility of the receptor. We compared the in vivo ligand effects with the ability of PR to carry out chromatin remodeling at the MMTV promoter in vitro. We found that ZK98229, a complete antagonist of PR, increases PR mobility in living cells, while the agonist R5020 decreases its rate of exchange on gene targets. in vitro, ZK98229 liganded receptor was unable to catalyze the SWI/SNF dependent displacement reaction, while R5020 occupied receptor was effective in the reaction. These findings suggest a direct role for chromatin remodeling in receptor movement in the nucleus.We developed an in vitro system to study nuclear receptor mobility. After permeablization of cells, we showed that receptor mobility was lost (for both PR and GR), but could be restored by the addition of highly purified molecular chaperones. In contrast, the equally mobile HP1a was refractory to addition of chaperones. These findings introduce a new paradigm for chaperone involvement in nuclear protein mobility.